This is an application for the Mentored Clinical Scientist Development Award to train Dr. Dana. Its main educational objective is to provide Dr. Dana with the structured program necessary for him to become an independent biomedical scientist in the area of ocular immunology and transplantation biology. The specific aims of the proposed educational program consist of Dr. Dana's active participation in 1) didactic graduate course work in immunology at Harvard Medical School, 2) weekly immunology seminars and conferences at the Schepens Eye Research Institute (SERI) and other medical affiliates of Harvard Medical School, and 3) a rigorous basic science research project under the supervision of Dr. Wayne Streilein, Professor and Vice Chair for Research of the Harvard Department of Ophthalmology, and Scientific Director of the SERI. The long-term objective of the research proposal is to help delineate some of the tissue, cellular, and molecular factors that account for the loss of the anterior segment's normal state of 'immune privilege' in corneal neovascularization. The specific aims of the project are: 1) controlled induction and regression of murine corneal neovascularization, 2) correlation of the degree of corneal lymphatic overflow with neovascularization, 3) delineation of the migratory and functionality profiles of Langerhans cells in inflamed and vascularized corneas, 4) assessment of the role of interleukin-1 and tumor necrosis factor-alpha in corneal neovascularization, and 5) delineation of the effects of these cellular and molecular mediators on corneal allograft survival. The study design relies on a precise and reproducible method for induction of neovascularization in the mouse via intrastromal implantation of pellets containing various angiogenic compounds. This will form the basis for a controlled induction of immunologic 'risk'. The overall health relevance of the proposed research is that immune rejection of corneal transplants is the leading cause for their failure. Research that contributes to our understanding of the cellular and molecular factors that impact on high-risk corneal transplantation can provide useful information for modulating those factors in ways that can engender graft longevity.